Research Organizations

Research Summary

The central interest of our laboratory is the mechanisms that initiate pancreatitis, a severe inflammatory disease that causes death in up to 5% of patients. The disease begins with the premature activation of pancreatic digestive enzymes within the acinar cell, inhibition of secretion, activation of inflammatory pathways, and cell death. We study the pathways that initiate disease with a goal of identifying therapeutic targets.

Extensive Research Description

We have found that this activation takes place in a special cellular organelle that has features of both a lysosome and classic secretory vesicle. We are characterizing this novel compartment and the second messenger signals that stimulate zymogen activation and are focusing on the role of vacuolar-ATPases (vATPase) and organelle acidification. vATPase are distinctive proton transporters that are dynamically regulated by assembly and disassembly of membrane-bound and soluble subunits.

We have found that distinct protein kinases, such as AMPK, regulate the activation and inactivation of the vATPase. These studies have direct clinical implications. Thus, we have recently found that an acute acid load worsens pancreatitis responses in an animal model of this disease. Further, certain metabolic products, such as lactate may lessen the severity of disease. Finally, pharmacological agents that enhance the activity of AMPK may be useful for disease treatment and/or prevention. We plan to pursue these studies using rodents models of pancreatitis, human acinar cells, and to collobrate with clinical investigators to examine these pathways in patients.

Mailing Address

Modal Title

How will my information be used?

When you express interest in a specific study, the information from your profile will be sent to the doctor conducting that study. If you're eligible to participate, you may be contacted by a nurse or study coordinator.

If you select a health category rather than a specific study, doctors who have active studies in that area may contact you to ask if you would like to participate.

In both cases, you will be contacted by the preferred method (email or phone) that you specified in your profile.